Trial Outcomes & Findings for Interventional Clinical Trial in Patients in Overactive Bladder With Nocturia in Women (NCT NCT01729819)

NCT ID: NCT01729819

Last Updated: 2018-09-12

Results Overview

A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

106 participants

Primary outcome timeframe

Baseline to 3 months of treatment

Results posted on

2018-09-12

Participant Flow

This was a multi-centre trial conducted in the US. A total of 33 sites were initiated in this trial, and of these eligible patients from 20 sites were randomised to a treatment. The first patient first visit was on 28 January 2013. The last patient last visit was on 19 November 2014.

The trial was initiated with a screening period of 3-4 weeks between Visits 1 and 2a, where no investigational medicinal product was taken. Patients who were on a prohibited medication and needed a wash-out period of 1-2 weeks initiated the trial at Visit 0. Eligible patients were randomised to one of the two treatment groups at Visit 2a.

Participant milestones

Participant milestones
Measure	Combination Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Overall Study STARTED	49	57
Overall Study COMPLETED	43	50
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Combination Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Overall Study Adverse Event	2	4
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	2	0
Overall Study Other reason	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

Interventional Clinical Trial in Patients in Overactive Bladder With Nocturia in Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg) + Desmopressin orally disintegrating tablets (25 µg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg)+ Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets	Total n=97 Participants Total of all reporting groups
Age, Continuous	55.3 Years STANDARD_DEVIATION 12.6 • n=5 Participants	51.8 Years STANDARD_DEVIATION 10.3 • n=7 Participants	53.4 Years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	52 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	42 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	38 Participants n=7 Participants	73 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Mean Number of Nocturnal Voids	3.38 Voids STANDARD_DEVIATION 0.97 • n=5 Participants	3.11 Voids STANDARD_DEVIATION 1.06 • n=7 Participants	3.24 Voids STANDARD_DEVIATION 1.02 • n=5 Participants
Mean Number of Day time Voids	9.69 Voids STANDARD_DEVIATION 1.35 • n=5 Participants	10.1 Voids STANDARD_DEVIATION 1.97 • n=7 Participants	9.91 Voids STANDARD_DEVIATION 1.71 • n=5 Participants
Mean Nocturnal Urine Volume	546 mL STANDARD_DEVIATION 281 • n=5 Participants	537 mL STANDARD_DEVIATION 278 • n=7 Participants	541 mL STANDARD_DEVIATION 278 • n=5 Participants
Mean Time to First Nocturnal Void	125 Minutes STANDARD_DEVIATION 44.6 • n=5 Participants	143 Minutes STANDARD_DEVIATION 56.1 • n=7 Participants	135 Minutes STANDARD_DEVIATION 51.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.

Outcome measures

Outcome measures
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Change in Mean Number of Nocturnal Voids From Baseline	-1.63 Voids Interval -1.94 to -1.32	-1.29 Voids Interval -1.57 to -1.0

SECONDARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

The time to first nocturnal void was defined as the time from going to bed with the intention of sleeping until first nocturnal void or until waking in the morning in the case there is no nocturnal void. The time to first void was calculated as the average over three consecutive 24-hour periods prior to the respective visits.

Outcome measures

Outcome measures
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Change in Mean Time to First Nocturnal Void From Baseline	118.19 Minutes Interval 88.53 to 147.85	100.19 Minutes Interval 72.67 to 127.72

SECONDARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

The mean nocturnal urine volume was derived from the three-day urine volume diary. The nocturnal volume was defined as the sum of the volumes for all nocturnal voids including the volume of the first morning void within 30 min of waking up in the morning.

Outcome measures

Outcome measures
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Change in Mean Nocturnal Urine Volume From Baseline	-156.6 mL Interval -212.88 to -100.37	-92.46 mL Interval -145.27 to -39.66

SECONDARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

Responder status was defined as ≥33% decrease in the mean number of nocturnal void and at least one night with no voids out of the 3-day diary period.

Outcome measures

Outcome measures
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Responder Status	0.40 Proportion of responders	0.29 Proportion of responders

SECONDARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

A nocturnal void was defined as a void occurring at least 5 minutes after going to bed, but before getting up the next morning. The mean estimate was the average over 3 consecutive 24-hour periods prior to the respective visit as captured in the voiding and sleep diary.

Outcome measures

Outcome measures
Measure	Combination n=97 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment Month 1	-0.19 Voids Interval -0.68 to 0.3	—
Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment Month 2	-0.44 Voids Interval -0.95 to 0.06	—
Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment Month 3	-0.43 Voids Interval -0.86 to 0.01	—
Onset of Effect as Seen in Change in Mean Number of Nocturnal Voids From Baseline for Each Visit During Three Months of Treatment Overall (during the three months)	-0.35 Voids Interval -0.78 to 0.08	—

SECONDARY outcome

Timeframe: Baseline to 3 months of treatment

Population: The FAS comprised of all randomised and exposed subjects with at least one efficacy assessment after treatment initiation. The FAS comprised of 97 subjects (45 in the combination group and 52 in the tolterodine group).

An electronic diary was used in the trial to document the impact on sleep quality (sleep rating scales). The sleep rating scales included three questions that ranged from 0 (poor) to 10 (good). The average of each question for each visit was summarised and the change from baseline was analysed longitudinally during the three months of treatment.

Outcome measures

Outcome measures
Measure	Combination n=45 Participants Tolterodine tartrate extended release capsules (4 mg)+ Desmopressin orally disintegrating tablets (25 μg) Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=52 Participants Tolterodine tartrate extended release capsules (4 mg) + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline From very tired to wide awake, how do you feel now	1.76 Score on scale Interval 1.31 to 2.21	1.33 Score on scale Interval 0.91 to 1.76
Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline Rate how refreshed you feel now	1.81 Score on scale Interval 1.37 to 2.24	1.46 Score on scale Interval 1.06 to 1.87
Change in the Impact on Sleep as Measured by the Sleep Rating Scales From Baseline Rate the quality of your sleep last night	1.95 Score on scale Interval 1.52 to 2.39	1.67 Score on scale Interval 1.27 to 2.08

Adverse Events

Combination

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Tolterodine

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Combination n=48 participants at risk Tolterodine tartrate extended release capsules + Desmopressin orally disintegrating tablets Tolterodine tartrate extended release capsules Desmopressin orally disintegrating tablets	Tolterodine n=55 participants at risk Tolterodine tartrate extended release capsules + Placebo orally disintegrating tablets Tolterodine tartrate extended release capsules Placebo orally disintegrating tablets
Gastrointestinal disorders Dry mouth	2.1% 1/48 • Number of events 1 • 3 months The safety analysis set included all patients who received at least one dose of IMP and had at least one safety assessment. The safety analysis set comprised of 103 patients (48 in the combination group and 55 in the tolterodine group).	10.9% 6/55 • Number of events 6 • 3 months The safety analysis set included all patients who received at least one dose of IMP and had at least one safety assessment. The safety analysis set comprised of 103 patients (48 in the combination group and 55 in the tolterodine group).
Nervous system disorders Headache	4.2% 2/48 • Number of events 2 • 3 months The safety analysis set included all patients who received at least one dose of IMP and had at least one safety assessment. The safety analysis set comprised of 103 patients (48 in the combination group and 55 in the tolterodine group).	9.1% 5/55 • Number of events 5 • 3 months The safety analysis set included all patients who received at least one dose of IMP and had at least one safety assessment. The safety analysis set comprised of 103 patients (48 in the combination group and 55 in the tolterodine group).

Additional Information

Clinical Development Support

Ferring Pharmaceuticals

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the Sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the Sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow the Sponsor to seek patent protection of the invention.
Publication restrictions are in place

Restriction type: OTHER